CORE--CELL BIOLOGY LABORATORY

镰刀患者的临床变异性很大。 细胞疾病。尽管阿尔法地中海贫血和胎儿血红蛋白水平 已被确定为临床严重程度的重要因素， 许多患者的临床病程不能根据 必须寻求这两个参数和其他因素。我们的 假设是仔细评估细胞和膜参数 例如变形性、密度分布和与内皮细胞粘附性 在同时接受临床问题评估的患者中 与镰状细胞疾病相关，可能为我们提供新的见解 膜或细胞异常与血管生成的关系 镰状细胞病的病理生理学。我们已经包括了这个核心 我们中心应用程序中的工具，以便我们可以添加特定的 我们临床和基础研究项目的生物物理测量和 加强我们将从这些项目中获得的信息。一个 已建立的细胞生物学-生物物理设施将用于研究 鬼魂和完整的红细胞的细胞变形性， TECHICON H-1原型机和红细胞内皮细胞的密度分布 使用一种新开发的临床适用的方法进行细胞黏附。 当检测到变形性或变形性显著异常时 粘附性，对这些细胞的进一步评估，或其中的血浆 这些牢房被暂停，将被承担。对于这些测量， 将使用微吸管试验来表征细胞中的缺陷。 变形或表征粘连异常和 将对全血和密度分级红进行分析 细胞。这个核心设施将是最多的临床项目 在以下方面有帮助：1.)羟基脲或丁酸的药物试验 儿童和成人，2。)急性胸腔综合征患者基线和 在他们的临床过程中，3。)中枢神经系统的患者 系统研究，4.)在生命的前三年，孩子们紧随其后， 5.)临床表现严重的患者与患者相比 有轻度疾病者，6)。和接受过骨髓移植的患者 移植。羟基脲治疗患者的研究将 尤其令人感兴趣，因为已知它们的红细胞具有戏剧性的 MCV的增加和膜/细胞的仔细表征 这些单元格的属性尚未执行。通过比较 结果我们在细胞生物学核心到临床病程中获得了 在研究中，我们希望确定患者的相对重要性 这些细胞变化是镰状细胞病的病理生理学基础。

There is a great deal of clinical variability in patients with sickle cell disease. Although alpha thalassemia and fetal hemoglobin levels have been identified as important factors in regard to clinical severity, the clinical course in many patients can not be explained based upon these two parameters and additional factors must be sought. Our hypothesis is that careful evaluation of cellular and membrane parameters such as deformability, density profile and adherence to endothelial cells in patients who are simultaneously being evaluated for clinical problems related to sickle cell disease, may provide new insights into the relationship between membrane or cellular abnormalities and the pathophysiology of sickle cell disease. We have included this core facility in our center application so that we can add specific biophysical measurements to our clinical and basic research projects and enhance the information we will derive from these projects. An established cell biology-biophysical facility will be used to investigate cell deformability by ektacytometry of ghosts and intact red blood cells, density profiles on a prototype Technicon H-1 and red cell-endothelial cell adherence using a newly developed, clinically applicable method. When significant abnormalities are detected in either deformability or adherence, further evaluation of these cells, or the plasma in which these cells were suspended, will be undertaken. For these measurements, a micropipette assay will be used to characterize the defects in cell deformation or to characterize the abnormalities in adherence and analysis will be done on whole blood as well as density fractionated red cells. The clinical projects which this core facility will be most helpful in are 1.) drug trials with hydroxyurea or butyric acid in children and adults, 2.) acute chest syndrome patients at baseline and throughout their clinical course, 3.) patients in the central nervous system study, 4.) children followed during the first three years of life, 5.) patients who have severe clinical manifestations compared to patients who have mild disease, 6.) and patients who have undergone bone marrow transplantation. The studies in patients treated with hydroxyurea will be of particular interest as their red cells are known to have a dramatic increase in MCV and careful characterization of the membrane/cellular properties of these cells has not been performed. By comparing the results we obtain in the cell biology core to the clinical course of patients under study, we hope to establish the relative importance of these cellular changes to the pathophysiology of sickle cell disease.